Tumoral Intraductal Neoplasms of the Bile Ducts Comprise Morphologically and Genetically Distinct Entities
ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE, vol.147, no.12, pp.1390-1401, 2023 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Volume: 147 Issue: 12
- Publication Date: 2023
- Doi Number: 10.5858/arpa.2022-0343-oa
- Journal Name: ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, CINAHL, EMBASE, Public Affairs Index
- Page Numbers: pp.1390-1401
- Istanbul University-Cerrahpasa Affiliated: Yes
Abstract
Context.-Tumoral (grossly visible) intraductal neo-plasms of the bile ducts are still being characterized. Objective.-To investigate their morphologic, immuno-histochemical, and molecular features.Design.-Forty-one cases were classified as gastric-, intestinal-, pancreatobiliary-type intraductal papillary neo-plasm (IPN), intraductal oncocytic papillary neoplasm (IOPN), or intraductal tubulopapillary neoplasm (ITPN) on the basis of histology. All neoplasms were subjected to targeted next-generation sequencing.Results.-The mean age at diagnosis was 69 years (42- 81 years); male to female ratio was 1.3. Most neoplasms (n = 23, 56%) were extrahepatic/large (mean size, 4.6 cm). The majority (n = 32, 78%) contained high-grade dysplasia, and 68% (n = 28) revealed invasion. All gastric-type IPNs (n = 9) and most ITPNs/IOPNs showed consistent colabeling for CK7/MUC6, which was less common among others (P = .004). Intestinal-type IPNs (n = 5) showed higher rates of CK20 expression than others (P , .001). Overall, the most commonly mutated genes included TP53 and APC, while copy number variants affected ELF3 and CDKN2A/B. All gastric-type IPNs contained an alteration affecting the Wnt signaling pathway; 7 of 9 (78%) showed aberrations in the MAPK pathway. Mutations in APC and KRAS were common in gastric-type IPNs as compared with others (P = .01 for both). SMAD4 was more frequently mutated in intestinal -type IPNs (P = .02). Pancreatobiliary-type IPNs (n = 14) exhibited frequent alterations in tumor suppressor genes including TP53, CDKN2A/B, and ARID2 (P = .04, P = .01 and P = .002, respectively). Of 6 IOPNs analyzed, 3 (50%) revealed ATP1B1-PRKACB fusion. ITPNs (n = 6) showed relatively few recurrent genetic aberrations. Follow-up information was available for 38 patients (median, 58.5 months). The ratio of disease-related deaths was higher for the cases with invasion (56% versus 10%).Conclusions.-Tumoral intraductal neoplasms of the bile ducts, similar to their counterparts in the pancreas, are morphologically and genetically heterogeneous.